Intracranial complications of sinogenic and otogenic infections in children: an ESPN survey on their occurrence in the pre-COVID and post-COVID era.

BACKGROUND: COVID-19 pandemic is thought to have changed the epidemiology of some pediatric neurosurgical disease: among them are the intracranial complications of sinusitis and otitis (ICSO). According to some studies on a limited number of cases, both streptococci-related sinusitis and ICSO would have increased immediately after the pandemic, although the reason is not clear yet (seasonal changes versus pandemic-related effects). The goal of the present survey of the European Society for Pediatric Neurosurgery (ESPN) was to collect a large number of cases from different European countries encompassing the pre-COVID (2017-2019), COVID (2020-2021), and post-COVID period (2022-June 2023) looking for possible epidemiological and/or clinical changes. MATERIAL AND METHODS: An English language questionnaire was sent to ESPN members about year of the event, patient's age and gender, presence of immune-deficit or other favoring risk factors, COVID infection, signs and symptoms at onset, site of primary infection, type of intracranial complication, identified germ, type and number of surgical operations, type and duration of medical treatment, clinical and radiological outcome, duration of the follow-up. RESULTS: Two hundred fifty-four cases were collected by 30 centers coming from 14 different European countries. There was a statistically significant difference between the post-COVID period (129 children, 86 cases/year, 50.7% of the whole series) and the COVID (40 children, 20 cases/year, 15.7%) or the pre-COVID period (85 children, 28.3 cases/year, 33.5%). Other significant differences concerned the presence of predisposing factors/concurrent diseases (higher in the pre-COVID period) and previous COVID infection (higher in the post-COVID period). No relevant differences occurred as far as demographic, microbiological, clinical, radiological, outcome, morbidity, and mortality data were concerned. Paranasal sinuses and middle ear/mastoid were the most involved primary site of infection (71% and 27%, respectively), while extradural or subdural empyema and brain abscess were the most common ICSO (73% and 17%, respectively). Surgery was required in 95% of cases (neurosurgical and ENT procedure in 71% and 62% of cases, respectively) while antibiotics in 99% of cases. After a 12.4-month follow-up, a full clinical and radiological recovery was obtained in 85% and 84% of cases, respectively. The mortality rate was 2.7%. CONCLUSIONS: These results suggest that the occurrence of ICSO was significantly increased after the pandemic. Such an increase seems to be related to the indirect effects of the pandemic (e.g., immunity debt) rather than to a direct effect of COVID infection or to seasonal fluctuations. ICSO remain challenging diseases but the pandemic did not affect the management strategies nor their prognosis. The epidemiological change of sinusitis/otitis and ICSO should alert about the appropriate follow-up of children with sinusitis/otitis.

Beneficial and harmful effects of physical activity on care-seeking for low back pain: the AUTBACK study.

PURPOSE: People who seek more care for low back pain (LBP) tend to experience poorer recovery (e.g. higher pain and disability levels). Understanding the factors associated with care-seeking for LBP might improve patient outcomes and potentially alleviate the burden of LBP on global health systems. This study aimed to investigate the relationship between different intensities, volumes, and domains of physical activity and care-seeking behaviours, in people with a history of LBP. METHODS: Longitudinal data from adult twins were drawn from the AUstralian Twin BACK study. The primary outcome was the total self-reported frequency (counts) of overall utilisation of care for LBP, over 1 year. Secondary outcomes were the utilisation of health services, and the utilisation of self-management strategies, for LBP (assessed as total frequency over 1 year). Explanatory variables were device-based measures of sedentary behaviour and moderate-to-vigorous intensity physical activity, and self-reported physical workload, and work, transport, household, and leisure domain physical activity, at baseline. RESULTS: Data from 340 individuals were included. Median age was 56.4 years (IQR 44.9-62.3 years) and 73% of participants were female. Medium-to-high baseline volumes of sedentary behaviour were significantly associated with greater counts of overall care utilisation (IRR 1.60, 95%CI 1.04-2.44) and utilisation of self-management strategies (IRR 1.60, 95%CI 1.02-2.50) for LBP, over 1 year. Medium-to-high baseline volumes of household domain physical activity were significantly associated with greater counts of utilising self-management strategies for LBP over 1 year (IRR 1.62, 95%CI 1.04-2.53). No explanatory variables were associated with the utilisation of health services for LBP. CONCLUSION: People who engage in higher baseline volumes of sedentary behaviour or physical activity in the household setting (e.g. housework, gardening, yard work, general household maintenance) utilise 1.6 times more care for LBP over 1 year. Findings suggest that higher volumes of these behaviours may be harmful for LBP. No intensities, volumes, or domains of physical activity demonstrated clear benefits for LBP. Where feasible, patients and clinicians should collaborate to screen and develop strategies to reduce engagement in sedentary behaviour or physical activity in the household setting. Contextual factors (e.g. patient symptom severity, sociocultural roles, occupational demands) should be considered when devising appropriate behaviour change strategies.

Effective moisture diffusivity prediction in two Portuguese fruit cultivars (Bravo de Esmolfe apple and Madeira banana) using drying kinetics data.

Air convective dehydration was performed at various temperatures (35 °C, 40 °C, 45 °C and 50 °C) using two types of fruits cultivars produced in different regions of Portugal: the Bravo de Esmolfe apple, from the Beiras province, and the Cavendish banana, from Madeira Island. The data collected were used to predict the effective moisture diffusion, which is a crucial input parameter in drying modeling and design. As expected, the values obtained in both falling drying rate periods detected for apples increased with an increase in drying temperature. The effective moisture diffusion in apples varied from 1.968 × 10-10 m2 s-1 at 35 °C to 4.013 × 10-10 m2 s-1 at 50 °C, for the first falling drying rate period, and from 0.9567 × 10-10 m2 s-1 at 35 °C to 3.328 × 10-10 m2 s-1 at 50 °C, for the second period. The dependence of effective moisture diffusion on temperature for bananas is similar, ranging from 1.572 × 10-10 to 2.627 × 10-10 m2 s-1 as the drying temperature changed from 35 to 50 °C.

Drying kinetics of two fruits Portuguese cultivars (Bravo de Esmolfe apple and Madeira banana): An experimental study.

Air convective dehydration was carried out at a laboratory scale using two fruits of cultivars produced in different regions of Portugal: Bravo de Esmolfe apple, from Beiras province, and Cavendish banana, from Madeira Island. Fresh fruits were dried in a tray drier with a hot airstream at different temperatures (35, 40, 45, and 50 °C) and velocity of 1.6 m s-1. Drying rate curves were obtained using a simple mathematical approach applied to the moisture content curves adjusting linear and polynomial functions. Different drying rate stages were noticed in the experiments made with apples (one constant drying rate period followed by two falling drying rate periods), while in the case of the banana the constant drying rate period was not perceived, being dried entirely during a unique falling drying rate period. As expected, the constant drying rate value obtained at the beginning of the experiments with apples is higher when these were conducted at higher temperatures, changing from 8.103 to 14.474 g m-2 s-1 when the airstream temperature increases from 35 to 50 °C. The correspondent critical moisture contents in the Bravo de Esmolfe apples, at the instant the constant drying rate period stops and the drying rate starts to fall, slightly decreases from 4.800 to 4.134 kgwater/kgdry solid. This study explored for the first time the drying behavior of these two important fruits that have been increasingly used in the food industry in Portugal, giving important information for the industrialization of its production.

Genetic variation within the human papillomavirus type 16 genome is associated with oropharyngeal cancer prognosis.

PURPOSE: A significant barrier to adoption of de-escalated treatment protocols for human papillomavirus-driven oropharyngeal cancer (HPV-OPC) is that few predictors of poor prognosis exist. We conducted the first large whole-genome sequencing (WGS) study to characterize the genetic variation of the HPV type 16 (HPV16) genome and to evaluate its association with HPV-OPC patient survival. PATIENTS AND METHODS: A total of 460 OPC tumor specimens from two large United States medical centers (1980-2017) underwent HPV16 whole-genome sequencing. Site-specific variable positions [single nucleotide polymorphisms (SNPs)] across the HPV16 genome were identified. Cox proportional hazards model estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival by HPV16 SNPs. Harrell C-index and time-dependent positive predictive value (PPV) curves and areas under the PPV curves were used to evaluate the predictive accuracy of HPV16 SNPs for overall survival. RESULTS: A total of 384 OPC tumor specimens (83.48%) passed quality control filters with sufficient depth and coverage of HPV16 genome sequencing to be analyzed. Some 284 HPV16 SNPs with a minor allele frequency ≥1% were identified. Eight HPV16 SNPs were significantly associated with worse survival after false discovery rate correction (individual prevalence: 1.0%-5.5%; combined prevalence: 15.10%); E1 gene position 1053 [HR for overall survival (HRos): 3.75, 95% CI 1.77-7.95; Pfdr = 0.0099]; L2 gene positions 4410 (HRos: 5.32, 95% CI 1.91-14.81; Pfdr = 0.0120), 4539 (HRos: 6.54, 95% CI 2.03-21.08; Pfdr = 0.0117); 5050 (HRos: 6.53, 95% CI 2.34-18.24; Pfdr = 0.0030), and 5254 (HRos: 7.76, 95% CI 2.41-24.98; Pfdr = 0.0030); and L1 gene positions 5962 (HRos: 4.40, 95% CI 1.88-10.31; Pfdr = 0.0110) and 6025 (HRos: 5.71, 95% CI 2.43-13.41; Pfdr = 0.0008) and position 7173 within the upstream regulatory region (HRos: 9.90, 95% CI 3.05-32.12; Pfdr = 0.0007). Median survival time for patients with ≥1 high-risk HPV16 SNPs was 3.96 years compared with 18.67 years for patients without a high-risk SNP; log-rank test P < 0.001. HPV16 SNPs significantly improved the predictive accuracy for overall survival above traditional factors (age, smoking, stage, treatment); increase in C-index was 0.069 (95% CI 0.019-0.119, P < 0.001); increase in area under the PPV curve for predicting 5-year survival was 0.068 (95% CI 0.015-0.111, P = 0.008). CONCLUSIONS: HPV16 genetic variation is associated with HPV-OPC prognosis and can improve prognostic accuracy.

[Acute oesophageal necrosis: A rare complication]. / Œsophagite nécrosante aiguë : une complication rare.

INTRODUCTION: Acute esophageal necrosis (AEN) is a rare medical disorder, which is characterized by a diffuse black esophageal mucosal during upper gastrointestinal endoscopy which is a highly recommended diagnostic tool. Its high mortality rate requires to be quickly evocated and an early management. CASE REPORT: We report a case of a 93-year-old patient with upper gastrointestinal bleeding. The upper endoscopy shows a grade D AEN according to the Los Angeles classification. Treatment consists of a parenteral nutritional support and an intravenous proton pump inhibitors treatment, which increase chances of a favorable outcome on endoscopic controls at 2 and 6 weeks. CONCLUSION: AEN has to be quickly evocated in a polyvascular and old patient with upper gastrointestinal bleeding. Our experience confirms that optimal and early management allow a esophageal complete healing at 6weeks.

Neuroendocrine pathways at risk? Simvastatin induces inter and transgenerational disruption in the keystone amphipod Gammarus locusta.

The primary focus of environmental toxicological studies is to address the direct effects of chemicals on exposed organisms (parental generation - F0), mostly overlooking effects on subsequent non-exposed generations (F1 and F2 - intergenerational and F3 transgenerational, respectively). Here, we addressed the effects of simvastatin (SIM), one of the most widely prescribed human pharmaceuticals for the primary treatment of hypercholesterolemia, using the keystone crustacean Gammarus locusta. We demonstrate that SIM, at environmentally relevant concentrations, has significant inter and transgenerational (F1 and F3) effects in key signaling pathways involved in crustaceans' neuroendocrine regulation (Ecdysteroids, Catecholamines, NO/cGMP/PKG, GABAergic and Cholinergic signaling pathways), concomitantly with changes in apical endpoints, such as depressed reproduction and growth. These findings are an essential step to improve hazard and risk assessment of biological active compounds, such as SIM, and highlight the importance of studying the transgenerational effects of environmental chemicals in animals' neuroendocrine regulation.

Persistent symptoms and decreased health-related quality of life after symptomatic pediatric COVID-19: A prospective study in a Latin American tertiary hospital.

OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19). METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.

Bioactive Coatings with Ag-Camphorimine Complexes to Prevent Surface Colonization by the Pathogenic Yeast Candida albicans.

Currently there is a gap between the rate of new antifungal development and the emergence of resistance among Candida clinical strains, particularly threatened by the extreme adhesiveness of C. albicans to indwelling medical devices. Two silver camphorimine complexes, [Ag(OH){OC10H14N(C6H4)2NC10H14O}] (compound P) and [{Ag(OC10H14NC6H4CH3-p)}2(µ-O)] (compound Q), are herein demonstrated as having high inhibiting activity towards the growth of Candida albicans and Candida glabrata clinical strains resistant to azoles, the frontline antifungals used in clinical practice. Compounds P and Q were also explored as bioactive coatings to prevent colonization by C. albicans and colonize the surface of indwelling medical devices, resulting in persistent infections. Functionalization of stainless steel with polycaprolactone (PCL) matrix embedded with compounds P or Q was reported for the first time to inhibit the colonization of C. albicans by 82% and 75%, respectively. The coating of PCL loaded with Q or P did not cause cytotoxic effects in mammalian cells, demonstrating the biocompatibility of the explored approach. The identification and further exploration of new approaches for surface engineering based on new molecules that can sensitize resistant strains, as herein demonstrated for complexes P and Q, is a significant step forward to improve the successful treatment of candidiasis.

Transferrin-functionalized lipid nanoparticles for curcumin brain delivery.

Curcumin is an anti-inflammatory and antioxidant compound with potent neuroprotective activity. Due to its poor water solubility, low bioavailability, rapid elimination and the challenges for crossing and transposing the blood-brain barrier (BBB), solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) loaded with curcumin were successfully produced and functionalized with transferrin, in order to mediate the transport of these particles through the BBB endothelium to the brain. The nanosystems revealed Z-averages under 200 nm, polydispersity index below 0.2 and zeta potential around -30 mV. Curcumin encapsulation around 65 % for SLNs and 80 % for NLCs was accomplished, while the functionalized nanoparticles presented a value around 70-75 %. A stability study revealed these characteristics remained unchanged for at least 3 months. hCMEC/D3 cells viability was firstly analysed by MTT and LDH assays, respectively, and a concentration of 10 µM of curcumin-loaded nanoparticles were then selected for the subsequent permeability assay. The permeability study was conducted using transwell devices with hCMEC/D3 cells monolayers and a 1.5-fold higher permeation of curcumin through the BBB was verified. Both SLNs and NLCs are promising for curcumin brain delivery, protecting the incorporated curcumin and targeting to the brain by the addition of transferrin to the nanoparticles surface.

The influence of lactation on BMD measurements and TBS: a 12-month follow-up study.

Although lactation is associated with transient bone loss and body weight changes, the unchanged TBS could highlight a limited effectiveness in detecting dynamic bone properties in the first year postpartum. PURPOSE: To evaluate trabecular bone score (TBS) and bone mineral density (BMD) in postpartum women. METHODS: This was a 12-month prospective cohort study with 40 lactating postpartum women and 44 non-pregnant women. The inclusion criteria were as follows: aged between 18 and 35 years old, an uncomplicated term (≥37 weeks) pregnancy with a single fetus, and no intention of becoming pregnant within 12 months. BMD measurements, including spine, hip, forearm and whole body, were performed by DXA at four different time points after delivery: (1) 1st month, (2) 3rd-4th month, (3) 6th-9th month, and (4) ≥ 12th month postpartum. RESULTS: BMD measurements showed a statistically significant decrease at spine (1.134 vs. 1.088 g/cm2, p < 0.01), femoral neck (0.988 vs. 0.946 g/cm2, p < 0.01), total femur (0.971 vs. 0.933 g/cm2, p < 0.01), and whole body (1.132 vs. 1.119 g/cm2, p = 0.03) at the 2nd assessment (peak of lactation). There was early spinal recovery after the 3rd assessment with complete recovery in all skeletal sites. Although it has had significant weight loss (67.3 vs. 63.2 kg, p < 0.01) and body mass index reduction (25.2 vs. 23.4, p < 0.01), there was significant increment of spine BMD (1.134 vs. 1.165 g/cm2, p < 0.01) after 12-month follow-up. The TBS did not change over time. CONCLUSIONS: Although lactation is associated with transient bone loss and body weight changes, the unchanged TBS could highlight a limited effectiveness in detecting dynamic bone properties in the first year postpartum.

Persistent symptoms and decreased health-related quality of life after symptomatic pediatric COVID-19: A prospective study in a Latin American tertiary hospital

OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19) METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.

Improvement of pure sensory mononeuritis multiplex and IgG1 deficiency with sitagliptin plus Vitamin D3.

INTRODUCTION: Mononeuritis multiplex (MM) is an unusual form of peripheral neuropathy involving at least two noncontiguous peripheral nerve trunks. The pure sensory form of MM occurs rarely. Immunoglobulin (Ig)G subclass deficiency is a clinically and genetically heterogeneous disorder. Up to 50% of adults with selective subnormal IgG1 levels or selective IgG1 deficiency have a concomitant autoimmune disorder. Herein, we report the case of a patient with MM and selective IgG1 deficiency who showed remarkable clinical improvement after 2-year combination therapy with the DPP-4 inhibitor sitagliptin plus vitamin D3. CASE REPORT: A 49-year-old man developed numbness in right hand and forearm. After 6 months, the patient developed left forefoot numbness. Approximately 8 years later, the patient started to develop numbness also in the right forefoot, along with symptoms of evening fatigue and occasional orthostatic hypotension. The patient also reported recurrent candidiasis in glans and intergluteal areas since adolescence. Electromyoneurography of lower and upper limbs revealed the presence of multiple mononeuropathies. Protein electrophoresis showed hypogammaglobulinemia and low serum IgG1 levels. Sural nerve biopsy showed the presence of perineuritis. The patient was diagnosed with MM due to perineuritis probably secondary to IgG1 deficiency. We, then, proposed combination therapy with sitagliptin and vitamin D3 in the attempt to achieve immunomodulation. At the last follow-up visit (2 years), the patient showed persistent clinical improvement, increase in IgG1 levels and normalization of protein electrophoresis. CONCLUSIONS: To the best of our knowledge, this is the first case showing a remarkable clinical improvement of MM and selective IgG1 deficiency achieved through a combination therapy with sitagliptin and vitamin D3.

Phlebotomines (Diptera: Psychodidae) and Mosquitoes (Diptera: Culicidae) Surrounding an Environmental Protection Zone in the Metropolitan Region of Natal: Use of Light-Emitting Diode (LED) Bulbs in Entomological Surveillance.

Entomological surveillance is very important for parasite and arbovirus vector control programs. Light traps with incandescent bulbs are used to attract insects and analyze the factors that contribute to the occurrence of species surrounding an environmental protection zone. Phlebotomine and mosquito abundance and their diversity were analyzed. Captures occurred monthly using six CDC light traps with two incandescent bulbs, two blue and two red LED lights. A total of 2211 phlebotomines of seven species and 4486 mosquitoes belonging to 20 taxa were captured. Different phlebotomine and mosquito species were found in the forest and peridomestic environments, with a predominance of the sand fly Evandromyia walkeri (Newstead) and the mosquito Coquillettidia venezuelensis (Theobald). There was a significant difference in the abundance of sand flies captured with the three bulbs tested, the blue bulb being the most efficient. The Shannon-Wiener diversity index showed that the trap equipped with a red LED light obtained a higher value than that of the blue LED and incandescent bulb. Analyses showed that the potential vectors and non-vectors of the two groups circulate between the forest and the peridomestic environment, suggesting an adaptation process of species to the altered environment. An incandescent light bulb can be substituted by an LED bulb, without compromising the sensitivity of the method. A blue LED is indicated for the abundant capture of mosquitoes and sand flies, while a red LED obtains a better result in terms of species diversity per capture.

Array-CGH: importance in the study of developmental delays in pediatrics. / Relevancia de los arrays de hibridación genómica comparada en el estudio de los retrasos del desarrollo en pediatría.

INTRODUCTION: Global developmental delay (GDD) is an intellectual and adaptive impairment in infants under 5 years of age who fail to meet expected developmental milestones. Intellectual disability is characterized by limitation in intellectual function and adaptive behavior, with onset in childhood. Frequent identifiable causes of GDD and intellectual disability are chromosomal imbalances. The array comparative genomic hybridization (aCGH) has contributed to improve the detection rate of genetic abnormalities and is considered the first-tier genetic test for unexplained intellectual disability. AIM: To analyze the results of a genetic study by aCGH due to GDD or intellectual disability in pediatric patients. PATIENTS AND METHODS: Retrospective analysis of pediatric patients followed in outpatient, which underwent a genetic study by aCGH, from 2012 to 2017. RESULTS: 215 patients were studied by aCGH. Of the total, 64.2% were investigated for intellectual disability and 35.8% for GDD. A 23.3% presented aCGH deletions or duplications, 56% for intellectual disability and 44% for GDD, with chromosomes 16, 22, 2 and 1 being the most implicated. CONCLUSION: Our study demonstrated a higher prevalence in males, according to previously published reports. The rate of detection abnormalities classified as pathogenic was higher than in other studies.

TITLE: Relevancia de los arrays de hibridación genómica comparada en el estudio de los retrasos del desarrollo en pediatría.Introducción. El retraso general del desarrollo (RGD) constituye un trastorno intelectual y del comportamiento adaptativo que aparece en los niños menores de 5 años que no consiguen alcanzar los hitos del desarrollo normal. La discapacidad intelectual se caracteriza por la limitación en el funcionamiento intelectual y en el comportamiento adaptativo, surgida en la infancia. Entre las causas frecuentes y reconocibles del RGD y de la discapacidad intelectual se encuentran los desequilibrios cromosómicos. Los arrays de hibridación genómica comparada (aCGH) han contribuido a mejorar la tasa de detección de las anomalías genéticas y ya se consideran la prueba genética de elección para la discapacidad intelectual de origen desconocido. Objetivo. Analizar los resultados del estudio genético con aCGH motivado por un RGD o una discapacidad intelectual en pacientes pediátricos. Pacientes y métodos. Análisis retrospectivo de pacientes pediátricos sometidos a seguimiento ambulatorio que fueron objeto de un estudio genético con aCGH entre 2012 y 2017. Resultados. El número de pacientes sometidos al estudio con aCGH ascendió a 215. Del total, el 64,2% fueron investigados por discapacidad intelectual, y el 35,8%, por RGD. El 23,3% presentó deleciones o duplicaciones en la aCGH; el 56%, por la discapacidad intelectual; y el 44%, por el RGD, y los cromosomas 16, 22, 2 y 1 fueron los implicados con más frecuencia. Conclusión. El presente estudio demuestra la mayor prevalencia de ambos en el sexo masculino, en consonancia con otras publicaciones precedentes. La tasa de detección de las anomalías clasificadas como patógenas resultó superior a la notificada en otros estudios.

RVG29-Functionalized Lipid Nanoparticles for Quercetin Brain Delivery and Alzheimer's Disease.

PURPOSE: Lipid nanoparticles (SLN and NLC) were functionalized with the RVG29 peptide in order to target the brain and increase the neuronal uptake through the nicotinic acetylcholine receptors. These nanosystems were loaded with quercetin to take advantage of its neuroprotective properties mainly for Alzheimer's disease. METHODS: The functionalization of nanoparticles with RVG29 peptide was confirmed by NMR and FTIR. Their morphology was assessed by transmission electron microscopy and nanoparticles size, polydispersity and zeta potential were determined by dynamic light scattering. The in vitro validation tests were conducted in hCMEC/D3 cells, a human blood-brain barrier model and thioflavin T binding assay was conducted to assess the process of amyloid-beta peptide fibrillation typical of Alzheimer's disease. RESULTS: RVG29-nanoparticles displayed spherical morphology and size below 250 nm, which is compatible with brain applications. Zeta potential values were between -20 and -25 mV. Quercetin entrapment efficiency was generally higher than 80% and NLC nanoparticles were able to encapsulate up to 90%. The LDH assay showed that there is no cytotoxicity in hCMEC/D3 cell line and RVG29-nanoparticles clearly increased in 1.5-fold the permeability across the in vitro model of blood-brain barrier after 4 h of incubation compared with non-functionalized nanoparticles. Finally, this nanosystem was capable of inhibiting amyloid-beta aggregation in thioflavin T binding assay, suggesting its great potential for neuroprotection. CONCLUSIONS: RVG29-nanoparticles that simultaneously target the blood-brain barrier and induce neurons protection against amyloid-beta fibrillation proved to be an efficient way of quercetin delivery and a promising strategy for future approaches in Alzheimer's disease. Graphical Abstract.

Low-trauma ankle fractures in Brazil: secular trends in patients over 50 years old from 2004 to 2013.

PURPOSE: The most common sites of low-energy trauma fractures are the femur, vertebra, humerus, and forearm. Ankle fractures have significant morbidity and high costs for surgical procedure. Forearm fractures are common nonvertebral fractures. Forearm fractures are classified as fragility fractures and predictive for fractures at other sites, although do not allow osteoporosis diagnosis. It is controversial whether ankle fractures are osteoporosis fractures. METHODS: Retrospective observational study, with secular trend analysis, in patients over 50 years old admitted in the Brazilian Public Health System, from 2004 to 2013. We collected hospitalization data according to the ICD-10 for low-trauma ankle and forearm fractures. Fracture rate was calculated according to gender, age, and geographic region, performed linear regression analysis, and estimated fracture rates for 2030. Comparison of ankle and forearm rates was also performed, grouping them in 3-year block. ANOVA test was used to compare each block. RESULTS: Ankle fracture rate was 21.39 fractures per 100,000 inhabitants, 23.98 in females and 18.49 in males. Fracture rates were higher in the South and Southeast regions. In absolute numbers, although ankle fracture rate increased with age, there was a significant decrease in the population over 80 years old. Data showed stabilization in ankle fractures from 2004 to 2013, in women and men. In 3-year block analysis, men had higher ankle fracture rates than forearm. However, in women, forearm rates were higher than ankle. CONCLUSION: Our data suggest that ankle fractures in men would be considered as a sentinel fracture with a similar clinical impact of forearm fracture.

Influence of adjacent teeth restored with metal posts in the detection of simulated internal root resorption using CBCT.

AIM: To assess the influence of artefacts generated by metal posts on the detection of simulated internal root resorption (IRR) in adjacent teeth using cone-beam computed tomography (CBCT) and to verify the impact of metal artefact reduction (MAR) on these cases. METHODOLOGY: CBCT images of 14 premolar teeth were acquired before and after IRR simulation using chemical and mechanical procedures, in an OP300 Maxio unit, with and without MAR. Each tooth was placed in the socket of a human mandible and scanned under three different conditions: (i) without adjacent teeth - control group; (ii) distal adjacent tooth restored with metal post; and (iii) with both adjacent teeth restored with metal post. Five oral radiologists scored the IRR detection using a 5-point scale. Diagnostic values were obtained for the tested groups and compared using two-way analysis of variance (α = 0.05). RESULTS: The presence of a single adjacent tooth restored with metal post did not significantly influence the diagnostic values for IRR detection (P > 0.05). The presence of both adjacent teeth with metal posts, without MAR application, was associated with a significantly lower area under the ROC curve (Az) compared to the control (P = 0.0182). In this case, the application of MAR increased Az, leading to nonsignificant differences from the control group and the group with one adjacent restored tooth (P > 0.05). Sensitivity decreased significantly when two adjacent restored teeth were present, regardless of MAR application (P = 0.0379). Specificity was not affected by the conditions tested (P > 0.05). CONCLUSION: CBCT detection of IRR was impaired by artefacts only when both adjacent teeth restored with metal posts were present. In such cases, activation of MAR improved the performance on this diagnostic task.